{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:40:57Z","timestamp":1784720457122,"version":"3.55.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"39","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Vaccine"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.vaccine.2021.08.032","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T09:33:42Z","timestamp":1629279222000},"page":"5548-5556","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":35,"title":["Safety and immunogenicity of intramuscularly administered CS6 subunit vaccine with a modified heat-labile enterotoxin from enterotoxigenic Escherichia coli"],"prefix":"10.1016","volume":"39","author":[{"given":"Tida","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro L.","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Maciel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Poole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla J.","family":"Testa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0094-248X","authenticated-orcid":false,"given":"Stefanie","family":"Trop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Duplessis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Riddle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Hamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Alcala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Prouty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-2606","authenticated-orcid":false,"given":"Rahsan","family":"Erdem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Louis Bourgeois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-1690","authenticated-orcid":false,"given":"Chad K.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0005","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/CMR.18.3.465-483.2005","article-title":"Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention","volume":"18","author":"Qadri","year":"2005","journal-title":"Clin Microbiol Rev"},{"issue":"7","key":"10.1016\/j.vaccine.2021.08.032_b0010","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.3201\/eid1107.041266","article-title":"Enterotoxigenic Escherichia coli and Vibrio cholerae diarrhea, Bangladesh, 2004","volume":"11","author":"Qadri","year":"2005","journal-title":"Emerg Infect Dis"},{"key":"10.1016\/j.vaccine.2021.08.032_b0015","article-title":"Considerations for using ETEC and Shigella disease burden estimates to guide vaccine development strategy","author":"Hosangadi","year":"2017","journal-title":"Vaccine"},{"key":"10.1016\/j.vaccine.2021.08.032_b0020","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1542\/peds.73.6.799","article-title":"Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh","volume":"73","author":"Black","year":"1984","journal-title":"Pediatrics"},{"issue":"5","key":"10.1016\/j.vaccine.2021.08.032_b0025","doi-asserted-by":"crossref","first-page":"707","DOI":"10.4269\/ajtmh.1999.61.707","article-title":"Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil","volume":"61","author":"Guerrant","year":"1999","journal-title":"Am J Trop Med Hyg"},{"issue":"5456","key":"10.1016\/j.vaccine.2021.08.032_b0030","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1126\/science.287.5456.1207","article-title":"Policy forum: public health. The health and wealth of nations","volume":"287","author":"Bloom","year":"2000","journal-title":"Science"},{"issue":"4","key":"10.1016\/j.vaccine.2021.08.032_b0035","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4269\/ajtmh.2009.80.609","article-title":"Global etiology of travelers' diarrhea: systematic review from 1973 to the present","volume":"80","author":"Shah","year":"2009","journal-title":"Am J Trop Med Hyg"},{"issue":"S2","key":"10.1016\/j.vaccine.2021.08.032_b0040","doi-asserted-by":"crossref","first-page":"4","DOI":"10.7205\/MILMED-D-17-00064","article-title":"Travelers' Diarrhea: An Update on the Incidence, Etiology, and Risk in Military Deployments and Similar Travel Populations","volume":"182","author":"Porter","year":"2017","journal-title":"Mil Med"},{"key":"10.1016\/j.vaccine.2021.08.032_b0045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40794-018-0077-1","article-title":"Travelers' diarrhea: update on the incidence, etiology and risk in military and similar populations - 1990\u20132005 versus 2005\u20132015, does a decade make a difference?","volume":"5","author":"Olson","year":"2019","journal-title":"Trop Dis Travel Med Vaccines"},{"issue":"4","key":"10.1016\/j.vaccine.2021.08.032_b0050","first-page":"370","article-title":"Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world","volume":"22","author":"Wenneras","year":"2004","journal-title":"J Health Popul Nutr"},{"issue":"S2","key":"10.1016\/j.vaccine.2021.08.032_b0055","doi-asserted-by":"crossref","first-page":"17","DOI":"10.7205\/MILMED-D-17-00068","article-title":"Antibiotic Therapy for Acute Watery Diarrhea and Dysentery","volume":"182","author":"Tribble","year":"2017","journal-title":"Mil Med"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0060","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"10.1016\/j.vaccine.2021.08.032_b0065","unstructured":"Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United States; 2019. https:\/\/www.cdc.gov\/drugresistance\/biggest-threats.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdrugresistance%2Fbiggest_threats.html."},{"key":"10.1016\/j.vaccine.2021.08.032_b0070","unstructured":"The Boston Consulting Group. Vaccines to tackle drug resistant infections: An evaluation of R&D opportunities; 2018. https:\/\/vaccinesforamr.org\/wp-content\/uploads\/2018\/09\/Vaccines_for_AMR.pdf."},{"key":"10.1016\/j.vaccine.2021.08.032_b0075","unstructured":"World Health Organization. Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance. https:\/\/www.who.int\/publications\/m\/item\/leveraging-vaccines-to-reduce-antibiotic-use-and-prevent-antimicrobial-resistance [2020 3\/31\/2021]."},{"key":"10.1016\/j.vaccine.2021.08.032_b0080","unstructured":"World Health Organization. DRAFT WHO Preferred Product Characteristics for Vaccines against Enterotoxigenic Escherichia coli; 2020. https:\/\/www.who.int\/immunization\/research\/ppc-tpp\/PPC_ETEC_April_2020_Public_Consultation.pdf [accessed 1\/21\/2021]."},{"issue":"6","key":"10.1016\/j.vaccine.2021.08.032_b0085","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1586\/erv.12.37","article-title":"Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans","volume":"11","author":"Zhang","year":"2012","journal-title":"Expert Rev Vaccines"},{"issue":"2","key":"10.1016\/j.vaccine.2021.08.032_b0090","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/infdis\/158.2.372","article-title":"Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial","volume":"158","author":"Clemens","year":"1988","journal-title":"J Infect Dis"},{"issue":"1","key":"10.1016\/j.vaccine.2021.08.032_b0095","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1017\/S0950268800029289","article-title":"Prospective study of diarrhoeal disease in a cohort of rural Mexican children: incidence and isolated pathogens during the first two years of life","volume":"101","author":"Cravioto","year":"1988","journal-title":"Epidemiol Infect"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0100","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1128\/iai.23.3.729-736.1979","article-title":"Immunity to enterotoxigenic Escherichia coli","volume":"23","author":"Levine","year":"1979","journal-title":"Infect Immun"},{"issue":"2","key":"10.1016\/j.vaccine.2021.08.032_b0105","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/infdis\/162.2.442","article-title":"Enterotoxins and adhesins of enterotoxigenic Escherichia coli: are they risk factors for acute diarrhea in the community?","volume":"162","author":"Lopez-Vidal","year":"1990","journal-title":"J Infect Dis"},{"issue":"1","key":"10.1016\/j.vaccine.2021.08.032_b0110","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1128\/JCM.38.1.27-31.2000","article-title":"Prevalence of toxin types and colonization factors in enterotoxigenic Escherichia coli isolated during a 2-year period from diarrheal patients in Bangladesh","volume":"38","author":"Qadri","year":"2000","journal-title":"J Clin Microbiol"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0115","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1086\/514227","article-title":"Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli","volume":"177","author":"Freedman","year":"1998","journal-title":"J Infect Dis"},{"issue":"19","key":"10.1016\/j.vaccine.2021.08.032_b0120","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1056\/NEJM198805123181904","article-title":"Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli","volume":"318","author":"Tacket","year":"1988","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.vaccine.2021.08.032_b0125","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1086\/338834","article-title":"Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay)","volume":"185","author":"Jiang","year":"2002","journal-title":"J Infect Dis"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0130","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.diagmicrobio.2009.10.002","article-title":"The epidemiology of travelers' diarrhea in Incirlik, Turkey: a region with a predominance of heat-stabile toxin producing enterotoxigenic Escherichia coli","volume":"66","author":"Porter","year":"2010","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"5","key":"10.1016\/j.vaccine.2021.08.032_b0135","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1111\/mmi.12044","article-title":"Crystal structure of enterotoxigenic Escherichia coli colonization factor CS6 reveals a novel type of functional assembly","volume":"86","author":"Roy","year":"2012","journal-title":"Mol Microbiol"},{"key":"10.1016\/j.vaccine.2021.08.032_b0140","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.01397-08","article-title":"Characterization and the studies of cellular interaction of native colonization factor CS6 purified from a clinical isolate of enterotoxigenic Escherichia coli","author":"Ghosal","year":"2009","journal-title":"Infect Immun"},{"issue":"42","key":"10.1016\/j.vaccine.2021.08.032_b0145","doi-asserted-by":"crossref","first-page":"5373","DOI":"10.1016\/j.vaccine.2008.07.091","article-title":"Role of different genes in the CS6 operon for surface expression of Enterotoxigenic Escherichia coli colonization factor CS6","volume":"26","author":"Tobias","year":"2008","journal-title":"Vaccine"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0150","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00788-18","article-title":"Biochemical and Immunological Evaluation of Recombinant CS6-Derived Subunit Enterotoxigenic Escherichia coli Vaccine Candidates","volume":"87","author":"Poole","year":"2019","journal-title":"Infect Immun"},{"issue":"2","key":"10.1016\/j.vaccine.2021.08.032_b0155","doi-asserted-by":"crossref","first-page":"e4487","DOI":"10.1371\/journal.pone.0004487","article-title":"Sulfatide recognition by colonization factor antigen CS6 from enterotoxigenic Escherichia coli","volume":"4","author":"Jansson","year":"2009","journal-title":"PLoS One"},{"issue":"37","key":"10.1016\/j.vaccine.2021.08.032_b0160","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1016\/j.vaccine.2011.06.084","article-title":"A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression","volume":"29","author":"Isidean","year":"2011","journal-title":"Vaccine"},{"issue":"1","key":"10.1016\/j.vaccine.2021.08.032_b0165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007037","article-title":"Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS)","volume":"13","author":"Vidal","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"10.1016\/j.vaccine.2021.08.032_b0170","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/ng.3145","article-title":"Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution","volume":"46","author":"von Mentzer","year":"2014","journal-title":"Nat Genet"},{"issue":"3","key":"10.1016\/j.vaccine.2021.08.032_b0175","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.vaccine.2020.12.034","article-title":"Evaluation of the immunogenicity and protective efficacy of a recombinant CS6-based ETEC vaccine in an Aotus nancymaae CS6 + ETEC challenge model","volume":"39","author":"Ramakrishnan","year":"2021","journal-title":"Vaccine"},{"issue":"11","key":"10.1016\/j.vaccine.2021.08.032_b0180","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00460-19","article-title":"Intradermal or Sublingual Delivery and Heat-Labile Enterotoxin Proteins Shape Immunologic Responses to a CFA\/I Fimbria-Derived Subunit Antigen Vaccine against Enterotoxigenic Escherichia coli","volume":"87","author":"Maciel","year":"2019","journal-title":"Infect Immun"},{"issue":"11","key":"10.1016\/j.vaccine.2021.08.032_b0185","doi-asserted-by":"crossref","first-page":"e0224073","DOI":"10.1371\/journal.pone.0224073","article-title":"Evaluation of the reactogenicity, adjuvanticity and antigenicity of LT(R192G) and LT(R192G\/L211A) by intradermal immunization in mice","volume":"14","author":"Maciel","year":"2019","journal-title":"PLoS One"},{"issue":"11","key":"10.1016\/j.vaccine.2021.08.032_b0190","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1128\/CVI.00464-13","article-title":"Safety and immunogenicity of a single oral dose of recombinant double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli","volume":"20","author":"El-Kamary","year":"2013","journal-title":"Clin Vaccine Immunol"},{"issue":"4","key":"10.1016\/j.vaccine.2021.08.032_b0195","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.vaccine.2018.12.011","article-title":"A Phase 1 dose escalating study of double mutant heat-labile toxin LTR192G\/L211A (dmLT) from Enterotoxigenic Escherichia coli (ETEC) by sublingual or oral immunization","volume":"37","author":"Bernstein","year":"2019","journal-title":"Vaccine"},{"key":"10.1016\/j.vaccine.2021.08.032_b0200","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103308","article-title":"Immune response characterization in a human challenge study with a Shigella flexneri 2a bioconjugate vaccine","volume":"66","author":"Clarkson","year":"2021","journal-title":"EBioMedicine"},{"issue":"2","key":"10.1016\/j.vaccine.2021.08.032_b0205","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00634-18","article-title":"Validation, and Application of a New World Primate Model of Enterotoxigenic Escherichia coli Disease for Vaccine Development","volume":"87","author":"Rollenhagen","year":"2019","journal-title":"Infect Immun"},{"issue":"45","key":"10.1016\/j.vaccine.2021.08.032_b0210","doi-asserted-by":"crossref","first-page":"7040","DOI":"10.1016\/j.vaccine.2020.09.025","article-title":"A first in human clinical trial assessing the safety and immunogenicity of transcutaneously delivered enterotoxigenic Escherichia coli fimbrial tip adhesin with heat-labile enterotoxin with mutation R192G","volume":"38","author":"Riddle","year":"2020","journal-title":"Vaccine"},{"issue":"49 Pt A","key":"10.1016\/j.vaccine.2021.08.032_b0215","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1016\/j.vaccine.2017.06.076","article-title":"Combination vaccine strategies to prevent enteric infections","volume":"35","author":"Walker","year":"2017","journal-title":"Vaccine"},{"issue":"8","key":"10.1016\/j.vaccine.2021.08.032_b0220","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.vaccine.2014.11.048","article-title":"Recommendations regarding the development of combined enterotoxigenic Eschericha coli and Shigella vaccines for infants","volume":"33","author":"Walker","year":"2015","journal-title":"Vaccine"},{"issue":"45","key":"10.1016\/j.vaccine.2021.08.032_b0225","doi-asserted-by":"crossref","first-page":"6695","DOI":"10.1016\/j.vaccine.2018.09.052","article-title":"Evaluation of a conjugate vaccine platform against enterotoxigenic Escherichia coli (ETEC), Campylobacter jejuni and Shigella","volume":"36","author":"Laird","year":"2018","journal-title":"Vaccine"},{"key":"10.1016\/j.vaccine.2021.08.032_b0230","unstructured":"World Health Organization. DRAFT WHO Preferred Product Characteristics for Vaccines against Shigella; 2020. https:\/\/www.who.int\/immunization\/research\/ppc-tpp\/PPC_Shigella_draft_for_review_april2020.pdf?ua=1 [accessed 03\/03\/2021]."}],"container-title":["Vaccine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0264410X21010653?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0264410X21010653?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T11:04:22Z","timestamp":1759403062000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0264410X21010653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":46,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["S0264410X21010653"],"URL":"https:\/\/doi.org\/10.1016\/j.vaccine.2021.08.032","relation":{},"ISSN":["0264-410X"],"issn-type":[{"value":"0264-410X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Safety and immunogenicity of intramuscularly administered CS6 subunit vaccine with a modified heat-labile enterotoxin from enterotoxigenic Escherichia coli","name":"articletitle","label":"Article Title"},{"value":"Vaccine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.vaccine.2021.08.032","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}